Identification of a set of genes associated with response to interleukin-2 and interferon-α combination therapy for renal cell carcinoma through genome-wide gene expression profiling

Mizumori,Osamu; Zembutsu,Hitoshi; Kato,Yoichiro; Tsunoda,Tatsuhiko; Miya,Fuyuki; Morizono,Takashi; Tsukamoto,Taiji; Fujioka,Tomoaki; Tomita,Yoshihiko; Kitamura,Tadaichi; Ozono,Seiichiro; Miki,Tsuneharu; Naito,Seiji; Akaza,Hideyuki; Nakamura,Yusuke

doi:10.3892/etm.2010.148

Identification of a set of genes associated with response to interleukin-2 and interferon-α combination therapy for renal cell carcinoma through genome-wide gene expression profiling

Authors:
- Osamu Mizumori
- Hitoshi Zembutsu
- Yoichiro Kato
- Tatsuhiko Tsunoda
- Fuyuki Miya
- Takashi Morizono
- Taiji Tsukamoto
- Tomoaki Fujioka
- Yoshihiko Tomita
- Tadaichi Kitamura
- Seiichiro Ozono
- Tsuneharu Miki
- Seiji Naito
- Hideyuki Akaza
- Yusuke Nakamura
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Affiliations: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan, Laboratory for Medical Informatics, Center for Genomic Medicine, RIKEN, Kanagawa 230-0045, Japan, Department of Urologic Surgery and Andrology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan, Department of Urology, Iwate Medical University, School of Medicine, Iwate 020-8505, Japan, Department of Urology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan, Department of Urology, Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan, Department of Urology, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan, Department of Urology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan, Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan, Department of Urology and Andrology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaragi 305-8577, Japan
Published online on: September 10, 2010 https://doi.org/10.3892/etm.2010.148
Pages: 955-961

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Abstract

Interleukin (IL)-2 and interferon (IFN)-α combination therapy for metastatic renal cell carcinoma (RCC) improves the prognosis for a subset of patients, while some patients suffer from severe adverse drug reactions with little benefit. To establish a method to predict responses to this combination therapy (approximately 30% response rate), the gene expression profiles of primary RCCs were analyzed using an oligoDNA microarray consisting of 38,500 genes or ESTs, after enrichment of the cancer cell population by laser microbeam microdissection. The analysis of 10 responders and 18 non-responders identified 24 genes that exhibited significant differential expression between the two groups. In addition, the patients whose tumors did not express HLA-DQA1 or HLA-DQB1 molecules demonstrated poor clinical response. Exclusion of patients with tumors lacking either of these two genes is likely to improve the response rate to IL-2 and IFN-α combination therapy from 30 to 67%, indicating that a simple pretreatment test provides useful information with which to subselect patients with renal cancer in order to improve the efficacy of this treatment and reduce unnecessary medical costs.

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